The long-range objectives of this research proposal are to study the roles of somatomedin (SM) in the regulation of growth and the pathogenesis of diabetes mellitus. Using a recently developed competitive protein binding assay for one of the SMs, NSILA, clinical studies are underway to determine the serum levels of NSILA in normal individuals of various weights, heights and ages, and in patients with various endocrine and metabolic disorders affecting growth, particularly diabetes mellitus. With respect to patients with diabetes mellitus, especial attention will be focused on those with vasculopathy in an effort to determine the possible etiologic role of SM in the pathogenesis of this disorder. Among the goals of this proposal are also to define the hormonal regulation of NSILA at the level of the target cells. Moreover, the biologic activity of NSILA in isolated cells, various organs and tissues, and intact organisms will be studied during the proposed grant period.